Purpose:
A canonical example of a neural computation is direction selectivity (DS) in the retina. At the level of the retinal output, direction selective ganglion cells respond strongly to visual motion in a preferred direction and weakly to motion in the opposite, null direction. Most DS ganglion cells are ON-OFF-type, and the source of DS is direction selective inhibitory input from presynaptic ON- and OFF-type starburst amacrine cells (SACs). While ON SACs have been studied intensely and a mechanism for their DS has been proposed, direct measurements of OFF SAC DS have been lacking and the underlying mechanism has not been explored. We hypothesized that OFF SAC DS differs from ON SAC DS, for two reasons. First, the dominant model for ON DS proposes a dendrite-autonomous mechanism including a soma-to-dendrite voltage gradient caused by tonic excitation. While tonic glutamate release is present at ON bipolar terminals, this model fails for OFF SACs because their presynaptic OFF bipolar cells lack tonic release. Second, recent EM reconstruction of the presynaptic OFF SAC circuit suggested a Reichardt-type correlation mechanism for OFF SACs, driven by sluggish central and fast peripheral dendritic excitation.

Results:
While imaging with the fluorescent biosensor iGluSnFR showed symmetric bipolar cell glutamate release for inward vs. outward radial motion, current and voltage responses in both ON and OFF SACs were distinctly asymmetric, with faster depolarization during outward motion. Circular white noise analysis of synaptic input across the SAC dendritic arbor showed substantial differences in the sign, amplitude, and spatial organization of inhibition in ON versus OFF SACs. Furthermore, OFF but not ON SACs showed a pronounced temporal gradient of excitatory input, with central excitation trailing peripheral excitation, consistent with the connectomic model. Model simulations showed that linear summation of temporally graded excitatory input across the dendritic arbor suffices for generating DS in OFF SACs.